help button home button Am J Pathol sign up for etoc
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Starczynski, J.
Right arrow Articles by Murray, P. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Starczynski, J.
Right arrow Articles by Murray, P. G.
(American Journal of Pathology. 2003;163:423-432.)
© 2003 American Society for Investigative Pathology

Variations in ATM Protein Expression During Normal Lymphoid Differentiation and Among B-Cell-Derived Neoplasias

Jane Starczynski*, William Simmons§, Joanne R. Flavell§, Phillip J. Byrd{ddagger}, Grant S. Stewart{ddagger}, Harjit S. Kullar{ddagger}, Alix Groom{ddagger}, John Crocker*, Paul A.H. Moss{ddagger}, Gary M. Reynolds, Meri Glavina-Durdov||, A. Malcolm R. Taylor{ddagger}, Christopher Fegan{dagger}, Tatjana Stankovic{ddagger} and Paul G. Murray§

From the Departments of Histopathology* and Haematology,{dagger} Birmingham Heartland’s Hospital, Birmingham, United Kingdom; the Cancer Research UK Institute for Cancer Studies,{ddagger} Department of Pathology,§ Division of Cancer Studies, and Liver Research Laboratories, University of Birmingham, Birmingham, United Kingdom; and the Department of Pathology,|| University Hospital Split, Split, Croatia

The ataxia telangiectasia mutated (ATM) protein plays a central role in the cellular response to DNA double-strand breaks (DSBs). Developmentally programmed DSBs are restricted to cellular subsets within lymphoid tissues and we asked whether ATM expression is differentially regulated during lymphoid differentiation. We showed that immature B cells in bone marrow and immature T cells of the thymic cortex were negative or weakly ATM-positive. T cells of thymic medulla and peripheral tissues strongly expressed ATM. High levels of ATM were present in the B lymphocytes of the mantle zone and in plasma cells, while the majority of germinal center B cells were negative or weakly labeled. Therefore, ATM expression appears to be down-regulated at those stages of lymphoid development where physiological DNA DSBs occur. In B-chronic lymphocytic leukemia and mantle cell lymphoma we observed two categories: ATM-negative tumors, most likely reflecting the presence of ATM mutation, and tumors with abundant ATM expression. Most follicular center-cell lymphomas and diffuse large B-cell lymphomas, which rarely show inactivation of the ATM gene, were negative or weakly ATM-positive. Tumor cells from most cases of Hodgkin’s disease were ATM-negative. Therefore, unless ATM inactivation occurs, ATM expression in lymphoid tumors is likely to reflect their cellular origin. As a result, immunostaining to identify lymphoid neoplasias with ATM inactivation might only be feasible for tumors derived from the stages where ATM is constitutively highly expressed.




This article has been cited by other articles:


Home page
 Nucleic Acids ResHome page
M. Mierau, G. A. Drexler, A. Kutzera, K. Braunschmidt, J. Ellwart, F. Eckardt-Schupp, E. Fritz, J. Bachl, and B. Jungnickel
Non-conservative homologous recombination in human B lymphocytes is promoted by activation-induced cytidine deaminase and transcription
Nucleic Acids Res., October 1, 2008; 36(17): 5591 - 5601.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
V. Stagni, M. G. di Bari, S. Cursi, I. Condo, M. T. Cencioni, R. Testi, Y. Lerenthal, E. Cundari, and D. Barila
ATM kinase activity modulates Fas sensitivity through the regulation of FLIP in lymphoid cells
Blood, January 15, 2008; 111(2): 829 - 837.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
B. Austen, A. Skowronska, C. Baker, J. E. Powell, A. Gardiner, D. Oscier, A. Majid, M. Dyer, R. Siebert, A. M. Taylor, et al.
Mutation Status of the Residual ATM Allele Is an Important Determinant of the Cellular Response to Chemotherapy and Survival in Patients With Chronic Lymphocytic Leukemia Containing an 11q Deletion
J. Clin. Oncol., December 1, 2007; 25(34): 5448 - 5457.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
G. S. Stewart, T. Stankovic, P. J. Byrd, T. Wechsler, E. S. Miller, A. Huissoon, M. T. Drayson, S. C. West, S. J. Elledge, and A. M. R. Taylor
RIDDLE immunodeficiency syndrome is linked to defects in 53BP1-mediated DNA damage signaling
PNAS, October 23, 2007; 104(43): 16910 - 16915.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
A. Dutton, C. B. Woodman, M. B. Chukwuma, J. I. K. Last, W. Wei, M. Vockerodt, K. R. N. Baumforth, J. R. Flavell, M. Rowe, A. M. R. Taylor, et al.
Bmi-1 is induced by the Epstein-Barr virus oncogene LMP1 and regulates the expression of viral target genes in Hodgkin lymphoma cells
Blood, March 15, 2007; 109(6): 2597 - 2603.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
B. Austen, J. E. Powell, A. Alvi, I. Edwards, L. Hooper, J. Starczynski, A. M. R. Taylor, C. Fegan, P. Moss, and T. Stankovic
Mutations in the ATM gene lead to impaired overall and treatment-free survival that is independent of IGVH mutation status in patients with B-CLL
Blood, November 1, 2005; 106(9): 3175 - 3182.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2003 by the American Society for Investigative Pathology.